AMG 487

Product NameAMG 487
CAS473719-41-4
MFC32H28F3N5O4
MW603.59
EINECS
MOL File473719-41-4.mol

Chemical Properties

Melting point	161.2℃ (ethyl acetate heptane )
storage temp.	Keep in dark place,Sealed in dry,Store in freezer, under -20°C
solubility	DMSO:41.0(Max Conc. mg/mL);67.93(Max Conc. mM)
form	A crystalline solid
color	White to yellow

Usage And Synthesis

Uses

N-[(1R)-1-[3-(4-Ethoxyphenyl)-3,4-dihydro-4-oxopyrido[2,3-d]pyrimidin-2-yl]ethyl]-N-(3-pyridinylmethyl)-4-(trifluoromethoxy)benzeneacetamide is a selective and potent antagonist of the chemokine receptor CXCR3.

Biological Activity

AMG 487 is an orally available, potent and selective chemokine (C-X-C motif) receptor 3 (CXCR3) antagonist (IC50 = 8/8.2 nM against CXCL10/11 (IP-10/ITAC) for CXCR3 binding) th at inhibits CXCR3 ligands-induced cell migration (CXCL10/11/9 IC50 = 8/15/36 nM). AMG 487 inhibits ITAC-induced calcium mobilization in vitro (IC50 = 5 nM) and reduces bleomycin-induced cellular lung recruitment in wild-type mice to the same level as in Cxcr3-deficient mice in vivo (3 mg/kg b.i.d. s.c.).

in vivo

AMG 487 (0.03-10 mg/kg, s.c.) exhibits significant reduction in cellular infiltration into the lungs in a dose dependent manner^[1].
AMG487 (5 mg/kg, s.c., twice daily) develops fewer metastases than that in vehicle-treated mice^[2].
AMG487 (5 mg/kg, s.c.)-treated mice exhibits fewer pulmonary nodules than the control mice in both the models. AMG487 reduces the tumour volume^[3].

IC 50

¹²⁵I-IP10-CXCR3: 8 nM (IC₅₀); ¹²⁵I-ITAC-CXCR3: 8.2 nM (IC₅₀)